Synthesis of 2′-deoxy-2′-fluororibo- and 2′-deoxy-2′,2′-difluororibonucleosides derived from 6-(het)aryl-7-deazapurines

• Published in: Tetrahedron 2012-09, Vol.68 (39), p.8300-8310
• Main Authors: Perlíková, Pavla, Jornet Martínez, Neus, Slavětínská, Lenka, Hocek, Michal
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Aromatic compounds; Bearing; Biological and medical sciences; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemical reactions; Chemistry; Cross coupling; Derivatives; Exact sciences and technology; Kinetics and mechanisms; Medical sciences; Nucleosides; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Pharmacology. Drug treatments; Preparations and properties; Reactivity and mechanisms; Synthesis; Tetrahedrons
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.07.033

A series of novel sugar-modified derivatives of cytostatic 6-hetaryl-7-deazapurine ribonucleosides (2′-deoxy-2′-fluororibo- and 2′-deoxy-2′,2-difluororibonucleosides) bearing an aryl or hetaryl group in position 6, was prepared and screened for biological activity. The fluororibo derivatives were prepared by aqueous palladium catalyzed cross-coupling reactions of the corresponding 6-chloro-7-deazapurine 2′-deoxy-2′-fluororibonucleoside 11 with (het)arylboronic acids. The key intermediate 11 was prepared by a six-step sequence from the corresponding arabinonucleoside by selective protection of 3′- and 5′-hydroxyls by acid-labile groups followed by stereoselective SN2 fluorination and deprotection. The difluororibo-series was prepared by non-stereoselective glycosidation of 6-chloro-7-deazapurine with benzoyl-protected 2-deoxy-2,2-difluoro-d-erythro-pentofuranosyl-1-mesylate followed by cross-couplings, separation of anomers and deprotection. The title nucleosides did not show considerable cytostatic or antiviral activity. [Display omitted]